scholarly journals Dihydropteroate synthase (DHPS) gene mutation study in HIV-Infected Indian patients with Pneumocystis jirovecii pneumonia

2010 ◽  
Vol 4 (11) ◽  
pp. 761-766 ◽  
Author(s):  
Anuj Kumar Tyagi ◽  
Bijay Ranjan Mirdha ◽  
Kalpana Luthra ◽  
Randeep Guleria ◽  
Anant Mohan ◽  
...  

Introduction: Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations' (55th and 57th codon) association with prior sulfa prophylaxis failure has been reported from both developed and developing countries. We conducted a prospective study to determine the prevalence of P. jirovecii DHPS mutations from 2006 to 2009 on P. jirovecii isolates obtained from HIV-infected patients with a clinical diagnosis of Pneumocystis carinii pneumonia (PCP) admitted to our tertiary care reference health center in New Delhi, India. Methodology: Detection of P. jirovecii cysts was performed by direct fluorescent antibody (DFA) staining and by Grocott's-Gomori methenamine silver staining (GMS). DNA detection was performed by polymerase chain reaction (PCR) using primers for the major surface glycoprotein (MSG) gene. P. jirovecii DHPS gene was amplified by nested PCR protocol and sequenced for detecting mutations at the 55th and 57th codons. Results: Out of 147 HIV-positive patients with suspected Pneumocystis pneumonia (PCP), 16 (10.8%) PCP positive cases were detected. Of 16 cases, nine (56.2%) were positive by DFA staining, four (25%) were positive by Grocott's-Gomori methenamine silver staining, and all 16 were positive by MSG PCR. DHPS mutations at the 55th and 57th codons were observed in 6.2% of HIV patients studied, which was relatively low compared to reports from developed nations. Conclusions:  Prevalence of Pneumocystis jirovecii DHPS mutations associated with cotrimoxazole treatment failure may be low in the Indian subpopulation of HIV-positive patients and warrants larger studies to elucidate the true picture of Pneumocystis jirovecii sulfa drug resistance in India.

Author(s):  
Shohreh AZIMI ◽  
Azar SABOKBAR ◽  
Amir BAIRAMI ◽  
Mohammad Javad GHARAVI

Background: Pneumocystis jirovecii pneumonia (PCP) remains a leading cause of mortality among HIV-infected patients. The aim of study was to find out P. jirovecii in versatile group of HIV-positive patients prisoners. Methods: Overall, 102 HIV positive patients from Ghezel Hesar Prison, Karaj, Iran from October 2016 to March 2017 without any respiratory symptoms were selected with different medication histories against HIV and PCP. Microscopic and molecular (qualitative real-time PCR) examination were applied on sputum specimens and serological investigation (β-D-glucan assay for fungal diseases) carried out on patient’s sera. Results: Only 3 and 1 patients were positive for PCP by microscopic and molecular testing, respectively. Twenty-four (23.5%) and 78 (76.5%) out of 102 patients were seropositive and seronegative for fungi disease, respectively. Seropositive patients were older than seronegative subjects (P<0.001). Most of seropositive individuals showed less mean value of CD4 counts compared to seronegative group (P<0.001). Of 54 patients who were under HIV therapy, 13 were seropositive compared to 11 out of 24 seropositives who were no adhere to treatment (P<0.001). In terms of prophylactic antibiotic therapy against PCP, of 24 patients who received prophylaxis, 3 (12.5%) and 21 (87.5%) were seropositive and seronegative, respectively (P<0.001). On the contrary, among 78 patients who did not receive prophylaxis, 21 (27%) and 57 (73%) belonged to seropositive and seronegative patients, respectively (P<0.001). Conclusion: There was no strong evidence for PCP infection/disease among symptomless, HIV positive patients. According to their mean CD4 counts, the hypothesis for being negative in a majority of applied tests would be the absence of severe immunosuppression in the patients.


2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Abigayle Sullivan ◽  
Theresa Lanham ◽  
Ronald Krol ◽  
Shilla Zachariah

We describe a rare case of Pneumocystis jirovecii pneumonia (PCP) in a heterosexual man with a pertinent medical history of well-controlled human immunodeficiency virus (HIV) on highly active antiretroviral therapy (HAART) and PCP prophylaxis with atovaquone. The patient presented with recurrent shortness of breath, worsening malaise, and fever, following treatment for hypersensitivity pneumonitis one month prior, including a twenty-four-day course of 40 milligrams daily glucocorticoid with taper. However, transbronchial biopsies, lavage, and cytology from prior admission were inconclusive. The patient refused video-assisted thoracic surgery (VATS) at that time. Upon readmission, bronchoscopy with right VATS and lung biopsy were performed. Grocott’s methenamine silver stain of right lung biopsy was positive for Pneumocystis jirovecii. This case is a rare example of PCP in a patient with a normal CD4 count (>487 cells/μL) and a low viral load (<20 copies/mL) despite PCP prophylactic antibiotics in the setting of recent iatrogenic immunosuppression.


Author(s):  
Arezoo BOZORGOMID ◽  
Yazdan HAMZAVI ◽  
Sahar HEIDARI KHAYAT ◽  
Behzad MAHDAVIAN ◽  
Homayoon BASHIRI

Background: The human immunodeficiency virus (HIV) is one of the greatest health challenges facing worldwide. The virus suppresses the immune system of the patient. The purpose of this study was to describe the epidemiology of Pneumocystis jirovecii colonization, rarely found in normal people, in patients with stage 4 HIV infection in Kermanshah, Iran, from Mar 1995 to Feb 2016. Methods: In this retrospective study, we surveyed medical records of stage 4 HIV-positive patients with Pneumocystis admitted to Behavioral Counseling Center of Kermanshah. Several parameters were analyzed including demographic characteristics, body mass index (BMI), treatment regimen, diagnostic methods, presenting signs and symptoms, presence of co-pathogens (bacteria, viruses, or fungi), and nadir of CD4 T-cell count before and after treatment. Results: During the study period, 114 HIV-positive patients were analyzed, of whom 93 were male and 21 were female, respectively. Of 114 cases, 26 (22.8%) patients had Pneumocystis. All 26 colonized patients had CD4 cell counts below 200 cells/mm3 (range 9–186). The median CD4 count increased from 91 cells/mm3 pretrimethoprim/sulfamethoxazole (TMP/SMX) to an estimated 263 cells/mm3 after starting (TMP/SMX). BMI was normal in the majority of the patients (85%) and coughs, sputum, and chest pain (19; 73%) followed by dyspnea, weakness, and lethargy (7; 27%) were the most common presentations of fungal pneumonia. Conclusion: HIV/AIDS-infected patients are an environmental reservoir of P. jirovecii infection that might transmit the infection from one person to another via the airborne route. In addition, rapid identification of such individuals may reduce the morbidity and mortality rate of this disease.


2021 ◽  
Author(s):  
wenzhang long ◽  
kunting xiao ◽  
yongqiang yuan

Abstract PurposeWe conducted a meta-analysis to evaluate the diagnostic performance of various levels of serum (1-3)-Beta-D-glucan(BDG) for Pneumocystis jirovecii(PJ) infection using Fungitell assay.MethodsEMBASE, MEDLINE, and the reference lists of relevant studies were identified up to March 12,2021, with no language restrictions. Meta-analysis was performed using random-effects models for bivariate analysis. Subgroup analyses were implemented in HIV-positive Pneumocystis jirovecii pneumonia (PJP), HIV-negative PJP, and PJP versus colonized patients.ResultsNineteen individual studies that included a total of 2,310 participants met our inclusion criteria. The overall sensitivity, specificity, positive likelihood ratio(LR+) and negative likelihood ratio (LR−),and 95 % confidence interval CI of serum-BDG were 0.94(95 % CI: 0.89–0.96),0.76 (95 % CI: 0.65–0.85), 3.99 (95 % CI: 2.59–6.13),0.08 (95 % CI: 0.05–0.15), respectively. Futher stratified analysis of diagnostic values showed that various levels of serum BDG differed in sensitivity, specificity, LR+ and LR− in the diagnosis of PJP. Subgroup analyses also indicated that the cutoff value of 200 pg/mL had sufficient diagnostic accuracy in HIV-positive PJP patients versus controls. Moreover, the 80 pg/mL cutoff value had satisfactory diagnostic accuracy in PJP versus colonized patients, a overall sensitivity of 0.86 (95% CI, 0.73-0.93), a overall specificity of 0.82(95% CI,0.73-0.88), a overall LR+ 4.70(95 % CI: 3.11–7.08), and a overall LR−0.17(95 % CI: 0.09–0.34),individually.ConclusionsThis meta-analysis suggests that the optimal positive threshold for serum BDG, tested by the Fungitell assay, requires better definition and clinical validation rather than the recommended cutoff of 80pg/mL by the manufacturer in the diagnosis of PJP. These cutoff values could be further refined in additional studies that focus on populations that are as homogeneous as possible.


2007 ◽  
Vol 14 (3) ◽  
pp. 165-168 ◽  
Author(s):  
Latha Menon ◽  
Rakesh Patel ◽  
Lakshmi Varadarajalu ◽  
Ernesto Sy ◽  
Gilda-Diaz Fuentes

2017 ◽  
Vol 13 (01) ◽  
pp. 002-009
Author(s):  
Dhulika Dhingra ◽  
Amitabh Singh ◽  
Anirban Mandal

Abstract Pneumocystis jirovecii (previously known as Pneumocystis carinii), a yeast-like, atypical fungus, is an important human pathogen especially in the immunocompromised hosts. It primarily causes pneumonia (P. jirovecii pneumonia or PJP), but rarely can infect other extrapulmonary sites, such as lymph nodes, spleen, liver, and bone marrow. Though an early age of colonization/infection has been documented even in healthy children, children with human immunodeficiency virus (HIV) infection, those with immunosuppression secondary to malignancies, cancer chemotherapy, and other immunosuppressive agents, and primary immunodeficiency are the ones primarily affected with the disease. The mode of presentation is variable depending on the underlying disease, immune status, and age of the patient, but clinical features of PJP are largely nonspecific. Though diffuse, perihilar predominant, bilaterally symmetrical interstitial infiltrates with apical sparing is characteristically seen in pulmonary imaging, it is very difficult to differentiate between PJP and other causes of pneumonia in immunocompromised hosts. The growth of the organism being extremely difficult in the laboratory, direct demonstration of the organism or its DNA in pulmonary secretions (induced sputum, bronchoalveolar lavage [BAL], etc.) by either direct stains or polymerase chain reaction (PCR) is the predominant mode of diagnosis. Chemoprophylaxis is indicated for HIV-infected infants and other children with profound immunosuppression. Co-trimoxazole is the drug of choice for both prophylaxis and therapy in children with PJP; pentamidine, atovaquone, dapsone, and clindamycin/primaquine are other alternatives. Following the advent of highly active antiretroviral therapy (HAART) for the treatment of HIV disease and co-trimoxazole prophylaxis, both the incidence of PJP and associated mortality have decreased dramatically in the developing regions. Developing countries still have very high morbidity and mortality with PJP, especially in HIV-infected children.


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